2-Decarboxy-2-hydroxymethyl-19,20-didehydro-13,14-dihydro-PG1 compounds

ABSTRACT

The present invention provides novel 2-decarboxy-2-hydroxymethyl-19,20-didehydro-13,14-dihydro-PG 1  compounds methods for their preparation and pharmacological use for the induction of prostaglandin-like effect.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a division of Ser. No. 26,066, filed Apr. 2, 1979, pending issuance as a U.S. Patent.

BACKGROUND OF THE INVENTION

The present invention relates to novel prostaglandin analogs. Particularly, these compounds are analogs of the prostaglandins wherein the C-20 - C-19 position is unsaturated, i.e., 19,20-didehydro-PG compounds. Most particularly, the present invention relates to novel 2-decarboxy-2-hydroxymethyl-19,20-didehydro-13,14-dihydro-PG₁ compounds, a disclosure of the preparation and use of which is incorporated here by reference from U.S. Pat. 4,228,104 filed Apr. 2, 1979.

PRIOR ART

Prostaglandin analogs exhibiting unsaturation in the C-17, C-18, or C-20 position are known in the art. See, for example, U.S. Pat. No. 3,919,285 German Offenlegungsschrift No. 2,635,985 (and its corresponding Derwent Farmdoc CPI No. 10302A), and U.S. Pat. No. 4,064,351 for examples of such compounds. See also the references cited in U.S. Ser. No. 26,066.

SUMMARY OF THE INVENTION

The present invention particularly provides:

A compound of the formula ##STR1## wherein D is:

(1) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,

(2) --(CH₂)₃ --CH₂ --CF₂ --,

(3) --(CH₂)₃ --O--CH₂ --,

(4) --(CH₂)₂ --O--(CH₂)₂ --,

(5) --CH₂ --O--(CH₂)₃ --, ##STR2## wherein g is zero, one, two, or three; wherein Q is ##STR3## wherein R₅ is hydrogen or methyl, wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl; wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; wherein W is ##STR4## and wherein X is --CH₂ CH₂ --.

Specific embodiments of the present invention include

2-decarboxy-2-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGF₁,

2-decarboxy-2-hydroxymethyl-11-deoxy-13,14-dihydro-19,20-didehydro-PGF.sub.1α,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxy-methyl-13,14-dihydro-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGF₂β,

2-decarboxy-2-hydroxymethyl-11-deoxy-13,14-dihydro-19,20-didehydro-PGF.sub.1β,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-11-deoxy-13,14-dihydro-19,20-didehydro-PGE.sub.1,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-1,3,14-dihydro-19,20-didehydro-PGE₁ ,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGE₁.

The compounds of the present invention are particularly useful for inducing prostaglandin-like biological effects, as is described in U.S. Ser. No. 26,066. Uses of compounds in accordance with the present invention include, therefore, anti-asthmatic indication. 

I claim:
 1. A compound of the formula ##STR5## wherein D is (1) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,(2) --(CH₂)₃ --CH₂ --CF₂ --, (3) --(CH₂)₃ --O--CH₂ --, (4) --(CH₂)₂ --O--(CH₂)₂ --, (5) --CH₂ --O--(CH₂)₃ --, ##STR6## wherein g is zero, one, two, or three; wherein Q is ##STR7## wherein R₅ is hydrogen or methyl, wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl; wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; wherein W is ##STR8## and wherein X is --CH₂ CH₂ --.
 2. A compound according to claim 1, wherein D is --(CH₂)₃ --(CH₂)_(g) --CH₂ --, wherein g is zero, one, two or three.
 3. A compound according to claim 2, wherein g is one.
 4. A compound according to claim 3, wherein W is ##STR9##
 5. A compound according to claim 4, wherein R₂ is hydroxyl.
 6. 2-Decarboxy-2-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGF₁α, a compound according to claim
 5. 7. A compound according to claim 4, wherein R₂ is hydrogen.
 8. 2-Decarboxy-2-hydroxymethyl-11-deoxy-13,14-dihydro-19,20-didehydro-PGF₁α, a compound according to claim
 7. 9. A compound according to claim 4, wherein R₂ is hydroxymethyl.
 10. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGF₁α, a compound according to claim
 9. 11. A compound according to claim 3, wherein W is ##STR10##
 12. A compound according to claim 11, wherein R₂ is hydroxyl.
 13. 2-Decarboxy-2-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGF.sub.2β, a compound according to claim
 12. 14. A compound according to claim 11, wherein R₂ is hydrogen.
 15. 2-Decarboxy-2-hydroxymethyl-11-deoxy-13,14-dihydro-19,20-didehydro-PGF₁β, a compound according to claim
 14. 16. A compound according to claim 14, wherein R₂ is hydroxymethyl.
 17. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxy-methyl-13,14-dihydro-19,20-didehydro-PGF₁β, a compound according to claim
 16. 18. A compound according to claim 3, wherein W is ##STR11##
 19. A compound according to claim 18, wherein R₂ is hydroxyl.
 20. 2-Decarboxy-2-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGE₁, a compound according to claim
 19. 21. A compound according to claim 18, wherein R₂ is hydrogen.
 22. 2-Decarboxy-2-hydroxymethyl-11-deoxy-13,14-dihydro-19,20-didehydro-PGE₁, a compound according to claim
 21. 23. A compound according to claim 18, wherein R₂ is hydroxymethyl.
 24. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGE₁, a compound according to claim
 23. 25. A compound according to claim 3, wherein W is ##STR12##
 26. A compound according to claim 25, wherein R₂ is hydroxyl.
 27. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-13,14-dihydro-19,20-didehydro-PGE₁, a compound according to claim
 26. 28. A compound according to claim 25, wherein R₂ is hydroxymethyl.
 29. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19,20-didehydro-PGE₁, a compound according to claim
 28. 